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Morphogen Pathways in Systemic Sclerosis

  • SCLERODERMA (J VARGA, SECTION EDITOR)
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Abstract

The morphogen pathways Wnt, hedgehog, and Notch are key regulators of organ development and tissue homeostasis. In adults, the tightly regulated activity of morphogen pathways is essential for cell renewal and tissue regeneration. Loss of control and persistent activation of morphogen pathways, however, can lead to a variety of diseases, including malignancy and fibrotic disorders. In recent years, pathological activation of Wnt, hedgehog, and Notch pathways have been described in systemic sclerosis (SSc) and other fibrotic diseases. Experimental models reveal that morphogen pathways drive fibroblast activation and collagen release. In these model systems, genetic or pharmacological blockade of morphogen pathways inhibits collagen release and reduces experimental fibrosis. Importantly, inhibitors for Wnt, hedgehog, and Notch are already in clinical evaluation, thereby emphasizing the translational implications of these findings. Further experimental studies, however, should deepen our knowledge before initiating clinical trials with inhibitors of morphogen pathways.

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Acknowledgments

Dr Beyer is a research scholar at the Interdisciplinary Center of Clinical Research in Erlangen (“Erstantragsstellerprogramm”). Dr Distler is the recipient of grant A40 of the Interdisciplinary Center of Clinical Research (IZKF) in Erlangen, grants from the Deutsche Forschungsgesellschaft, and the Career Support Award of Medicine of the Ernst Jung Foundation.

Disclosure

Dr Distler has served on boards for Celgene Corp., Bayer, and JB Therapeutics; has served as a consultant and received honoraria from Celgene Corp., Bayer, JB Therapeutics, Boehringer Ingelheim GmbH, BioPharma, Active Biotech, Actelion Pharmaceuticals Ltd., Pfizer, Ergonex Pharma GmbH, and Bristol-Myers Squibb; has received payment for development of educational presentations (including service on speakers’ bureaus) from Celgene Corp., Bayer, JB Therapeutics, Boehringer Ingelheim GmbH, BioPharma, Active Biotech, Actelion Pharmaceuticals Ltd., Pfizer, Ergonex Pharma GmbH, Roche, and Bristol-Myers Squibb; and has held stock/stock options from 4D Science GmbH (a company by which his wife has also been employed). Dr Beyer reported no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany

    Christian Beyer & Jörg H. W. Distler

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  1. Christian Beyer
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Correspondence to Christian Beyer.

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This article is part of the Topical Collection on Scleroderma

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Beyer, C., Distler, J.H.W. Morphogen Pathways in Systemic Sclerosis. Curr Rheumatol Rep 15, 299 (2013). https://doi.org/10.1007/s11926-012-0299-6

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